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Pathologic microvasculature plays a key role in the leading causes of blindness including diabetic retinopathy, retinal vein occlusions, and macular degeneration. Current treatments, including laser therapy, photodynamic therapy (PDT), and anti-vascular endothelial growth factor (VEGF) therapy, impose significant burdens on patients, their families, and our health system because of frequent administration,...
Multi-frequency transducers may have a number of emerging applications including multi-scale imaging, superharmonc contrast imaging and imaging-therapy applications. For imaging-therapy applications low-frequencies are typically needed for therapeutic heating or contrast agent destruction, while higher-frequencies are required for high-resolution imaging. However, development of these multi-frequency...
Arbitrary excitation waveforms are desirable in HIFU array systems. In trans-skull therapy this is necessary to compensate for phase aberrations and achieve even heating of the skull. To facilitate this, wave form generators and large, costly class A RF amplifiers are used. High element counts are commonplace and so the portability of these systems is greatly reduced. We propose using switched mode...
Microembolization during PCI for acute myocardial infarction can cause microvascular obstruction (MVO). MVO severely limits the success of reperfusion therapies and is linked to worse prognosis, including death. A recent clinical trial showed that adjunct short pulse MB+US therapy prior to and following PCI in first STEMI patients, improved angiographic recanalization prior to PCI and ejection fraction...
The primary aim of this work was to develop and study the potential of Capacitive Micro-machined Ultrasound Transducers (CMUTs) for dual-mode ultrasound therapy and imaging. This was investigated in the context of Ultrasound-guided High Intensity Focused Ultrasound (USgHIFU) designed for endocavitary HIFU tissue ablation of the prostate gland. The hypothesis is that this CMUT design could offer potential...
Catheter-delivered ultrasound has been widely utilized for intravascular therapies such as thrombolysis, drug delivery, and plaque removal. High amplitude pressure is required for cavitation induced-microstreaming, which is considered main factor for therapeutic efficiency. Precise spatiotemporal control of insonation is important to relieve concerns on ultrasound-induced damaging of surrounding healthy...
Oxygen microbubbles (OMBs) have recently been used as adjunct treatment for solid tumors. Indeed, their ability to relieve tumor hypoxia was shown to benefit sonodynamic and other treatment outcomes in vivo. However, OMBs are often administered via intratumoral injection, and the effect of repeated OMB injections in tumors has not been investigated. Here we report on the paradoxical finding that daily...
Assessing the response of heart failure (HF) patients to Cardiac Resynchronization Therapy (CRT) currently relies on the ECG and left ventricular (LV) ejection fraction. Electromechanical Wave Imaging (EWI) is a high frame-rate (2000 Hz) ultrasound-based technique capable of non-invasively mapping the electromechanical activation in all four cardiac chambers in vivo. In this study, we aim to show...
Laser-generated focused ultrasound (LGFU) is a promising modality for micro-precision therapy, relying on cavitation-induced mechanical disturbance. However, conventional LGFU systems still require a high laser energy (several to tens of mJ/pulse), irradiated onto an optoacoustic lens, to generate a focal pressure sufficient for acoustic cavitation at focus. Acoustic attenuation over the tissue depth...
Detection of focused ultrasound (FUS)-stimulated microbubble activity (i.e. acoustic cavitation) is a key methodology for monitoring and guidance of FUS therapies that harness the bioeffects of acoustic cavitation. The intensity and location of secondary acoustic emissions emitted by microbubbles can be passively detected and imaged using diagnostic imaging arrays. In turn, ultrasound-guided FUS (USgFUS)...
We have developed a modern array driver employing multi-channel arbitrary waveform generator and linear amplifiers for transmit wavefront synthesis. The system utilizes deep waveform memory that can be configured for switching between transmit patterns seamlessly thus allowing for the use of spatial and frequency diversity in image acquisition. In this paper, we present the first experimental results...
The abnormal vasculature of tumor and the resulting abnormal microenvironment is a major barrier to optimal chemotherapeutic drug delivery. It is well known that ultrasound (US) can increase the permeability of the tumor vessel walls and enhance the accumulation of anticancer drugs. Reconstituted high density lipoproteins (rHDL) nanoparticles (NPs) allow selective delivery of anticancer agents to...
Volumetric dynamic contrast-enhanced ultrasound (DCE-US) can be used to yield 3D parametric maps to assess spatial changes in tumor perfusion heterogeneity during cancer treatment. Here, quantitative image features (texture and histogram-based features) extracted from 3D parametric maps were evaluated as surrogates of treatment response, and compared to conventional perfusion parameters.
Recently, the diffraction-limit of resolution for ultrasound imaging has been bypassed in-vivo with the localization of microbubbles [Errico et al, Nature 2015]. However, ultrasound therapy remains bound to the half-wavelength limit, imposing a compromise between the therapeutic precision and its penetration. Exploiting threshold phenomena, such as vaporization or cavitation, could provide a solution...
Tumor hypoxia has been shown to decrease the sensitivity of solid tumors to radiation. Systemic efforts to increase tumor oxygenation levels immediately prior to therapy, however, have largely proven unsuccessful. The objective of this work was to determine the utility of oxygen-filled, ultrasound sensitive microbubbles for locally delivering oxygen and sensitizing tissue to radiation in a breast...
Thermal ablation provides local control of cancer; however, pairing ablation with immunotherapy is attractive as there is emerging evidence that focal therapy enhances the efficacy of immunotherapy. The goals of local treatment are to rapidly debulk the tumor and release tumor antigen to stimulate immune recognition. We seek to evaluate combination protocols and their tumor suppressive effects.
Transarterial chemoembolization (TACE) is a standard care for patients with Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma (HCC) and may also be used as a bridging therapy in patients who are potential transplant candidates. Incomplete treatment is defined as the persistence of enhancing areas inside the treated lesions seen at the first imaging study after locoregional treatment....
Pancreatic cancer is an aggressive disease a 5-year-survival rate less than 7%. To improve the patient overall survival, recent developments in pancreatic cancer research have been targeting various components of the tumor microenvironment such as the extracellular matrix, blood vessels and immune cells. We hypothesize that targeted therapies will affect the biomechanics of the tumor microenvironment...
Previously, we reported on the development and clinical evaluation of an ultrasound image-guided laparoscopic high-intensity focused ultrasound (HIFU) probe for kidney tumor ablation compatible with an 18mm trocar. Since then, the relentless march towards miniaturization of laparoscopic tools has led to the obsolescence of this trocar size, prompting a re-design of the probe to accommodate market...
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